Structural study of three o-hydroxyacetophenone derivatives using X-ray powder diffraction: Interplay of weak intermolecular interactions

Article abstract of DOI:10.1039/c1ce05920c

A family of three o-hydroxyacetophenone derivatives, 2-hydroxy-5-methoxy-4- methylacetophenone (1), 5-methoxy-4-methyl-2-(phenylmethoxy)acetophenone (2) and 2-O-(α-methyl carboethoxy)-5-methoxy-4-methyl-acetophenone (3) were synthesized and their crystal structures were solved using laboratory X-ray powder diffraction data along with a detailed analysis of the Hirshfeld surfaces and 2D-fingerprint plots, facilitating a comparison of intermolecular interactions. The DFT optimized molecular geometries in 1 and 3 agree closely with those obtained from the crystallographic studies. In 2, however, the relative orientation of the two planar phenyl rings as established by the X-ray analysis and quantum mechanical calculations differs by 34.9°. The crystal packing in the compounds is stabilized by an interplay of weak hydrogen bonds, such as C-H...O, C-H...π and π...π interactions, forming supramolecular assemblies. The intermolecular C-H...O hydrogen bonds in 1-3 generate C11(6) chains and R_mⁿ(X) rings, which are further connected through C-H...π hydrogen bonds and π...π interactions to produce parallel molecular sheets built by fused R22(24) rings in 1, a three-dimensional architecture with C22(16)[R22(6)][R22(14)] synthons in 2, and a two-dimensional columnar framework in 3.

Full text of DOI:10.1039/c1ce05920c

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links <
C
CrystEngComm
Cite this: CrystEngComm, 2012, 14, 837
www.rsc.org/crystengcomm
PAPER
Structural study of three o-hydroxyacetophenone derivatives using X-ray
powder diffraction: interplay of weak intermolecular interactions†
a
Basab Chattopadhyay, Soumen Ghosh, Swastik Mondal,‡ Monika Mukherjee and Alok K. Mukherjee
b
a
a
b
*
Received 19th July 2011, Accepted 2nd October 2011
DOI: 10.1039/c1ce05920c
A family of three o-hydroxyacetophenone derivatives, 2-hydroxy-5-methoxy-4-methylacetophenone
(1), 5-methoxy-4-methyl-2-(phenylmethoxy)acetophenone (2) and 2-O-(a-methyl carboethoxy)-5-
methoxy-4-methyl-acetophenone (3) were synthesized and their crystal structures were solved using
laboratory X-ray powder diffraction data along with a detailed analysis of the Hirshfeld surfaces and
2D-fingerprint plots, facilitating a comparison of intermolecular interactions. The DFT optimized
molecular geometries in 1 and 3 agree closely with those obtained from the crystallographic studies. In
2, however, the relative orientation of the two planar phenyl rings as established by the X-ray analysis
and quantum mechanical calculations differs by 34.9ꢀ. The crystal packing in the compounds is
stabilized by an interplay of weak hydrogen bonds, such as C–H/O, C–H/p and p/p interactions,
forming supramolecular assemblies. The intermolecular C–H/O hydrogen bonds in 1–3 generate
C11(6) chains and Rmn(X) rings, which are further connected through C–H/p hydrogen bonds and p/
p interactions to produce parallel molecular sheets built by fused R22(24) rings in 1, a three-dimensional
architecture with C22(16)[R22(6)][R22(14)] synthons in 2, and a two-dimensional columnar framework in 3.
a rigid core with multiple donor atoms and having different
substitutions, and to study their structural features as well as the
interplay of weak interactions in building possible supramolec-
ular assemblies.
Introduction
Non-covalent molecular interactions, which include hydrogen
bonds and aromatic p-stacking interactions, are of fundamental
importance in the field of crystal engineering.1 Although strong
hydrogen bonds, such as O/N–H/O/N with an estimated
interaction energy in the range of 16–50 kJ molꢁ1, have long been
recognized as the key factor for providing the requisite robust-
ness and reproducible supramolecular synthon,2 it is becoming
increasingly evident that weak interactions, such as C–H/O and
C–H/p hydrogen bonds and p/p stacking, can also be deci-
sive in controlling the molecular assembly in organic
compounds.3 These interactions are individually weaker and
geometrically less well-defined, however, their combined effect
can be equally important as strong interactions.4 Desiraju and
coworkers have demonstrated various supramolecular synthons
based on C–H/O interactions.5,6 The effectiveness of C–H/p
hydrogen bonds has been reviewed on the basis of crystallo-
graphic findings and Cambridge Structural Database (CSD)
analyses.7 It is thus useful to design new compounds comprising
In this respect, substituted hydroxyacetophenones possessing
a number of C–H donors and a C]O acceptor constitute an
ideal structural motif with a rigid core. In addition to their uses in
the synthesis of plastics, agrochemicals and fragrances, several
o-hydroxyacetophenone derivatives exhibit anti-inflammatory,
cytotoxic and choleretic activities.8 A search of the Cambridge
Structural Database (version 5.32, November CSD 2010 release)9
for o-hydroxyacetophenone derivatives returned 63 hits
(excluding duplicate structure determination). If we restrict our
search with acyclic substitution at the 4 and 5 positions of the
acetophenone ring and the 2 position being occupied by an OH
or OCH3 group, only seven structures with the codes
DACHQO,10 DEKYIC01,11 DEKYOI,12 MXDABZ10,13 SOB-
NUT,14 VOXPED15 and XOZGEZ16 are found. The crystal
structures of all seven compounds mentioned above have been
determined using single-crystal X-ray analysis.
Although single-crystal X-ray diffractometry is the method of
choice for determination of crystal structures of molecular
compounds, an intrinsic limitation of this method is the
requirement to obtain single crystals of appropriate size and
quality that make them amenable to structure analysis. With the
recent developments in direct-space approaches for structure
solution,17 ab-initio crystal structure analysis of molecular solids
can now-a-days be accomplished from X-ray powder diffraction
data;18 significant challenges may, however, arise when the
aDepartment of Solid State Physics, Indian Association for the Cultivation
of Science, Jadavpur, Kolkata, 700032, India
bDepartment of Physics, Jadavpur University, Jadavpur, Kolkata, 700032,
India. E-mail: akm_ju@rediffmail.com; Fax: +9133 24146484; Tel: +9133
24148917
† CCDC reference numbers 835292–835294. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/c1ce05920c
‡ Present Address: Laboratory of Crystallography, University of
Bayreuth, 95440 Bayreuth, Germany
This journal is ª The Royal Society of Chemistry 2012
CrystEngComm, 2012, 14, 837–846 | 837

View Article Online
molecule possesses considerable flexibility or there are multiple
molecules in the asymmetric unit.19 Unlike single-crystal
diffractometry, which reveals the structure of the particular
crystal selected for data collection, X-ray powder diffraction
provides structural information of the bulk material.
(s, 3H, –COCH3), 3.8 (s, 3H, –OCH3), 6.7 (s, 1H, Ar–H), 6.9 (s,
1H, Ar–H), 12.0 (s, –OH); 13C NMR (75 MHz, CDCl3) d 17.2
(Ar–CH3), 26.9 (Ar–OCH3), 56.2 (Ar–COC*H3), 109.9 (]C–),
117.4 (]C–), 120.4 (]C–), 138.8 (]C–), 150.7 (]C–), 157.4 (]
C–), 203.7 (–C]O). Compound (2): m. p. 376 (2) K. Elemental
analysis found: C 75.48, H 6.39%; calculated for C17H18O3: C
75.55, H 6.66%. Spectroscopic analysis: IR 1664 cmꢁ1; 1H NMR
(300 MHz, CDCl3) dH 2.3 (s, 3H, Ar–CH3), 2.6 (s, 3H, –COCH3),
3.8 (s, 3H, –OCH3) 5.1 (s, 2H, Ar–CH2–), 6.9 (s, 1H, Ar–H) 7.3
(s, 1H, Ar–H), 7.36–7.45 (m, 5H, Ar–H); 13C NMR (75 MHz,
CDCl3) d 16.7 (Ar–CH3), 32.2 (–O–CH3), 55.6 (–COC*H3), 71.3
(Ar–CH2–), 110.8 (Ar–H), 116.0 (Ar–H), 125.8 (Ar–H), 127.5
(Ar–H), 128.1 (Ar–H), 128.6 (Ar–H), 133.5 (Ar–H), 136.5 (Ar–
H), 151.8 (Ar–H), 152.6 (Ar–H), 198.6 (Ar–H). Compound (3):
m.p. 412(2) K. Elemental analysis found C 63.66, H 6.74%;
calculated for C14H18O5: C 63.15, H 6.81%. Spectroscopic
analysis: 1H NMR: (300 MHz, CDCl3) dH 1.30 (t, J ¼ 7.1, 3H, C–
CH3), 2.20 (s, 3H, Ar–CH3), 2.71 (s, 3H, –COCH3), 4.29 (m, 2H,
–CO2–CH2–), 4.70 (s, 2H, –OCH2CO2–); 13C NMR (75 MHz,
CDCl3) d 14.1 (–CH3), 16.7 (Ar–CH3), 32.1(Ar–OCH3), 55.7
(Ar–CO–C*H3), 61.4 (–CO2C*H2CH3), 66.3 (–O–CH2–CO2–),
111.1 (Ar–H), 115.6 (Ar–H), 126.2 (Ar–H), 133.5 (Ar–H), 151.5
(Ar–H), 126.2 (Ar–H), 133.5 (Ar–H), 151.5 (Ar–H), 152.4 (Ar–
H), 168.5 (–CO–), 198.7 (–CO2–).
This idea prompted us to investigate the structural features of
o-hydroxyacetophenone derivatives using X-ray powder
diffraction and to analyze the role of weak hydrogen bonds in
building possible supramolecular assemblies. The synthesis and
crystallographic analysis of three o-hydroxyacetophenone
compounds, 2-hydroxy-5-methoxy-4-methylacetophenone (1),
5-methoxy-4-methyl-2-(phenylmethoxy)acetophenone (2) and
2-O-(a-methyl carboethoxy)-5-methoxy-4-methylacetophenone
(3) with powder diffraction data are described in the present
paper along with the DFT calculations to study the molecular
geometry. An investigation of close intermolecular interactions
in compounds 1–3 via Hirshfeld surface analysis is also
presented.
Experimental
Synthesis
The compound (1) was synthesized following the procedure
described by Sabui and Venkateswaran.20 A mixture of 2,5-
dihydroxy-4-methylacetophenone (30 mmol), anhydrous potas-
sium carbonate (32.6 mmol), methyl iodide (45 mmol) and
acetone (60 mL) was refluxed for 6 h. The mixture was cooled to
room temperature (300 K) and the excess acetone was distilled
off. The residue was poured into water (40 mL) and extracted
with dichloromethane (60 mL). The organic extract was washed
with water (40 mL), dried and concentrated to obtain a yellowish
solid, which on purification by column chromatography through
silica gel (60–120 mesh) using ethyl acetate/petroleum ether
(1 : 5) as eluent afforded the compound, 2-hydroxy-5-methoxy-
4-methyl acetophenone (1), as a crystalline powder (yield 90%).
Although compound (2) has been reported by Hauser and
Ganguly21 as an intermediate product during enantioselective
total synthesis of aminohydroxy epoxybenzoxocin, we followed
a new method for the syntheses of 5-methoxy-4-methyl-2-(phe-
nylmethoxy)acetophenone (2) and 2-O-(a-methyl carboethoxy)-
5-methoxy-4-methyl-acetophenone (3). A magnetically stirred
mixture of 2-hydroxy-5-methoxy-4-methyl acetophenone (1) (5.5
mmol), anhydrous K2CO3 (6.6 mmol) and KI (catalytic amount)
in dry acetone (25 mL) was added dropwise to benzyl bromide
for 2 (6.6 mL) and to a-bromo-ethyl-acetate for 3 (6.6 mL) at
room temperature. The reaction mixture was allowed to reflux
with stirring for 10 h. After cooling, most of the solvent was
removed and diluted with water. Simultaneous extraction was
performed with ether. The ether extract was washed with brine,
water, and dried. The yellowish residue was chromatographed
through silica gel with ethyl acetate/petroleum ether (1 : 3 in 2
and 1 : 10 in 3), as eluent affording 5-methoxy-4-methyl-2-
(phenylmethoxy)acetophenone (2) and 2-O-(a-methyl carboe-
thoxy)-5-methoxy-4-methyl-acetophenone (3) as crystalline
solids (yield: 80% for 2 and 70% for 3). Compound (1): m. p. 381
(2) K. Elemental analysis found: C 66.36, H 6.43%; calculated for
C10H12O3: C 66.67, H 6.67%. Spectroscopic analysis: IR: 1660
cmꢁ1; 1H NMR: (300 MHz, CDCl3) dH 2.2 (s, 3H, Ar–CH3), 2.5
X-Ray powder diffraction
Since our initial attempts to grow single crystals of appropriate
size and quality were not successful, the structure determination
of 1–3 was contemplated from X-ray powder diffraction. The
sample was ground to a fine homogenous powder using agate
pestle and mortar, and mounted in a top-loaded sample holder
fitted with a silicon monocrystal zero background plate (supplied
by Bruker AXS, Germany). X-Ray powder diffraction data of
ꢀ
1–3 were recorded at ambient temperature (20 C) on a Bruker
D8 Advance diffractometer, equipped with parallel (soller) slits,
ꢀ
CuKa1 radiation (l ¼ 1.5406 A) from a primary beam Ge(111)
monochromator and a Na(Tl)I scintillation detector, operating
in the Bragg-Brenteno geometry. Fixed slits were used: diver-
gence 0.6 mm, antiscatter 0.6 mm, and receiving 0.1 mm.
Diffraction data were collected over the 2q range of 5–100ꢀ with
a step width of 0.02ꢀ and a counting time of 25 s per step.
The 2q positions of the first 20 peaks in the diffraction profiles
were identified using the derivative based algorithm as imple-
mented in the peak search utility of the TOPAS 3.0 software
package.22 The indexing of the powder patterns of 1–3 carried
out using the program DICVOL0423 indicates monoclinic unit
ꢀ
ꢀ
ꢀ
cells with a ¼ 9.796(4) A, b ¼ 13.754(9) A, c ¼ 8.162(3) A, and
b ¼ 123.35(4)ꢀ [M(20) ¼ 26.5, F(20) ¼ 52.4 (0.0112, 34)] for 1,
ꢀ
ꢀ
ꢀ
a ¼ 12.144(5) A, b ¼ 16.436(5) A, c ¼ 7.481(2) A, and b ¼ 102.80
(3)ꢀ [M(20) ¼ 29.0 F(20) ¼ 63.5 (0.0064, 49)] for 2, and a ¼ 8.024
ꢀ
ꢀ
ꢀ
ꢀ
(3) A, b ¼ 7.264(2) A, c ¼ 23.98(2) A, and b ¼ 95.71(4) [M(20) ¼
15.7, F(20) ¼ 37.4(0.0107, 50)] for 3. Statistical analysis of the
powder patterns using the FINDSPACE module of EXPO
200424 indicated P21/c as the most probable space group for 1–3,
which was used for structure solution. To assess the choices of
the unit cell and the space group and to estimate the shape and
width of Bragg reflections along with the instrumental shifts, a Le
Bail fitting25 was performed using the program TOPAS 3.0. The
838 | CrystEngComm, 2012, 14, 837–846
This journal is ª The Royal Society of Chemistry 2012

View Article Online
profile fitting procedure, which makes no reference to any
structural model, was carried out by describing the peak shape
with a split-type pseudo-Voigt function.26 For the asymmetry
correction, the Berar-Baldinozzi function27 was used. The final
The starting atomic coordinates were taken from the final X-ray
refinement cycle. The geometries of the molecules were optimized
using the hybrid exchange–correlation functional BLYP35 and
a double numeric plus polarization (DNP) basis set.
values of Rp ¼ 0.0335, Rwp ¼ 0.0518 for 1, Rp ¼ 0.0463, Rwp
¼
0.0629 for 2, and Rp ¼ 0.0517 and Rwp ¼ 0.0737 for 3 confirm the
validity of the space group and the unit cell determined by
DICVOL04. The crystal structures of 1–3 were solved by global
optimization of structural models in direct-space based on
a Monte Carlo search using the simulated annealing technique
(in parallel tempering mode), as implemented in the program
FOX.28 The initial molecular geometry input in FOX was
determined by the MOPAC 5.0 program.29 The atomic coordi-
nates obtained from FOX were used as the starting model for the
Rietveld refinement using the GSAS program package30 with an
EXPGUI31 interface. The lattice parameters, background coef-
ficients and profile parameters were refined initially followed by
the refinement of positional coordinates of all non-hydrogen
atoms with soft constraints on bond lengths and bond angles,
and planar restraints on the phenyl moieties. The background
was described by the shifted Chebyshev function of first kind
with 36 points regularly distributed over the entire 2q range. A
Hirshfeld surface analysis
Hirshfeld surfaces36 and the associated 2D-fingerprint plots37
were calculated using CrystalExplorer.38 Bond lengths to
hydrogen atoms were set to typical neutron values (O–H ¼ 0.983
ꢀ
ꢀ
A, C–H ¼ 1.083 A). For each point on the Hirshfeld isosurface,
two distances de, the distance from the point to the nearest
nucleus external to the surface, and di, the distance to the nearest
nucleus internal to the surface, are defined. The normalized
contact distance (dnorm) based on de and di is given by:
ðdi-rivdw
Þ
ðde-revdw
Þ
dnorm
¼
þ
rivdw
revdw
vdW
with rivdW and re
being the van der Waals radii of the atoms.
The value of dnorm is negative or positive depending on the
intermolecular contacts being shorter or longer than the van der
Waals separations. The parameter dnorm displays a surface with
a red-white-blue color scheme, where bright red spots highlight
shorter contacts, white areas represent contacts around the van
der Waals separation, and blue regions are devoid of close
contacts.
2
ꢀ
fixed isotropic displacement parameter of 0.04 A for all non-
hydrogen atoms was maintained. Hydrogen atoms were placed
2
ꢀ
in the calculated positions with a common Biso value of 0.06 A .
In the final stage of refinement, a preferred orientation correction
was applied using the generalized spherical harmonic model, and
the order of spherical harmonics necessary to describe the
preferred orientation was 10 in 1, 14 in 2, and 12 in 3. The crystal
data and relevant refinement parameters of 1–3 are summarized
in Table 1. Selected bond lengths and bond angles obtained from
both powder-crystal structure analysis and DFT calculations are
listed in Table 2. Hydrogen bond distances (X-ray determined
and neutron normalized) calculated using PLATON32 are given
in Table 3.
Results and discussion
The compounds 1–3 consist of an acetophenone core with
a methyl and a methoxy substituent at the 4 and 5 positions,
respectively (Scheme1). The essential difference among the
compounds is that the hydroxyl group at the 2-position in 1 is
replaced by a phenylmethoxy moiety in 2 and an ethyl-2-
hydroxyacetate group in 3. The molecular views with the atom
labelling scheme and the Rietveld plots of 1–3 are shown in Fig. 1
and 2, respectively. The molecules of 1 and 3 are essentially
Computational study
ꢀ
ꢀ
planar with r.m.s. deviations of 0.05 A and 0.04 A, respectively.
The overall molecular conformation in 1 can be described by the
relative orientation of the hydroxyl and acetaldehyde groups,
which facilitates intramolecular O3–H3/O1 hydrogen bonding.
In 2, however, the planar benzyl moiety (C11–C17) is rotated
The isolated molecule DFT calculations were performed with full
geometry optimization without any symmetry restriction. All
calculations were carried out using the Dmol3 code33 in the
framework of a generalized-gradient approximation (GGA).34
Table 1 Crystal data and structure refinement parameters for C10H12O3 (1), C17H18O3 (2) and C14H18O5 (3)
(1)
(2)
(3)
Chemical formula
Mr
C10H12O3
180.20
C17H18O3
270.33
C14H18O5
266.29
T/K
Crystal system, space group, Z
295(2)
Monoclinic, P21/c, 4
9.8702(15), 13.7735(19), 8.1460(12)
123.368(5)
924.9(3)
1.294
295(2)
Monoclinic, P21/c, 4
12.207(6), 16.487(8), 7.495(4)
102.952(5)
1470.0(13)
1.221
295(2)
Monoclinic, P21/c, 4
8.0139(5), 7.2616(3), 23.9540(18)
95.738(5)
1386.99(16)
1.275
ꢀ
a, b, c/A
b/ꢀ
Volume/A
3
ꢀ
D/mg mꢁ3
Wavelength/A
ꢀ
1.5406
1.5406
1.5406
Data, restraints, parameters
Rp
Rwp
R(F2)
c2
4750, 78, 123
0.0465
0.0659
0.0978
9.68
4790, 122, 173
0.0579
0.0855
0.1208
6.66
4800, 126, 152
0.0496
0.0751
0.1208
3.35
This journal is ª The Royal Society of Chemistry 2012
CrystEngComm, 2012, 14, 837–846 | 839

View Article Online
ꢀ
ꢀ
Table 2 Selected bond lengths (A) and angles ( ) for C10H12O3 (1), C17H18O3 (2) and C14H18O5 (3)
1
2
3
Bonds/angles
XRD
DFT
XRD
DFT
XRD
DFT
O1–C7
O2–C5
O2–C9
O3–C2
O3–C11
O4–C12
O5–C12
O5–C13
C–C (ph)mean
C–C (others)mean
C1–C7–O1
C8–C7–O1
C6–C5–O2
C4–C5–O2
C1–C2–O3
C3–C2–O3
C5–O2–C9
C2–O3–C11
C12–C11–O3
C11–C12–O5
C12–O5–C13
C–C–C (ph)mean
1.257(4)
1.378(3)
1.427(3)
1.349(3)
1.258
1.388
1.439
1.355
1.201(5)
1.367(5)
1.419(5)
1.352(5)
1.398(5)
1.237
1.387
1.442
1.383
1.461
1.205(4)
1.379(4)
1.416(4)
1.366(4)
1.408(4)
1.195(4)
1.330(4)
1.454(4)
1.396(4)
1.508(3)
119.7(4)
118.4(4)
115.5(3)
124.8(3)
120.9(3)
119.2(3)
119.2(4)
120.3(4)
108.7(3)
111.8(4)
123.5(4)
120.0(3)
1.236
1.386
1.442
1.388
1.427
1.214
1.367
1.477
1.406
1.518
118.9
119.5
115.5
124.4
118.1
122.3
117.5
118.1
108.7
108.1
115.6
119.9
1.406(3)
1.513(3)
118.5(4)
117.2(4)
121.0(3)
119.0(3)
120.2(3)
118.3(3)
124.0(4)
1.41
1.50
1.390(4)
1.496(5)
118.4(4)
120.6(4)
118.7(3)
121.3(3)
119.3(4)
120.7(4)
119.6(4)
118.9(4)
118.7(3)
1.401
1.513
119.3
119.2
115.5
124.4
118.0
122.4
117.5
118.7
114.1
121.0
118.5
124.7
114.8
122.4
118.1
118.0
120.0(3)
119.9
120.0(3)
119.9
with respect to the substituted acetophenone fragment (C1–C10,
O1–O3) by 48.5(3)ꢀ. The torsion angle C2–O3–C11–C12 of 177.1
(5)ꢀ in 2 shows an anti configuration of the molecule about the
C11–O3 bond. The ethylhydroxyacetate side chain in 3 adopts
a fully extended trans configuration, the torsion angles C2–O3–
C11–C12, C11–C12–O5–C13 and C12–O5–C13–C14 are 179.5
(1)ꢀ, 178.9(1)ꢀ and 179.8(1)ꢀ, respectively.
Scheme 1
The molecular-orbital optimizations with Dmol3 corroborates
an almost trans configuration of the phenylmethoxy (in 2) and
ethylhydroxyacetate (in 3) groups with respect to the acetophe-
none core. An overlay of the molecular conformation of the title
compounds as determined by X-ray powder diffraction analyses
and theoretical calculations is shown in Fig. 3. The overall
molecular geometry in 1 and 3 as established by the quantum
Table 3 Intermolecular C–H/X (X ¼ O, p) hydrogen bonds and p/ p interactions in C10H12O3 (1), C17H18O3 (2) and C14H18O5 (3)a
D–H/A/ꢀ
Symmetry code
ꢀ
D–H/A
ꢀ
ꢀ
Interaction
H/A/A
D/A/A
(1)
C3–H3/O1
1
X-ray
0.95
1.08
0.97
1.08
2.40
2.27
2.56
2.46
3.307(10)
3.307(10)
3.431(8)
3.431(8)
162
161
150
148
ꢁx, ꢁ /2 + y, 1/2 ꢁ z
Norm-H
X-ray
Norm-H
C9–H9B/O3
1 + x, y, z
(2)
C9–H9B/O2
X-ray
Norm-H
X-ray
Norm-H
X-ray
Norm-H
X-ray
Norm-H
X-ray
Norm-H
0.96
1.08
0.97
1.08
0.97
1.08
0.97
1.08
0.97
1.08
2.52
2.43
2.56
2.45
2.57
2.46
2.85
2.75
2.95
2.86
3.344(7)
3.344(7)
3.498(9)
3.498(9)
3.472(5)
3.472(5)
3.681(5)
3.681(5)
3.621(7)
3.621(7)
144
142
163
162
156
155
146
144
130
128
ꢁ1 ꢁ x, ꢁy, 1 ꢁ z
ꢁx, ꢁy, 1 ꢁ z
C11–H11A/O1
C8–H8B/Cg1
C9–H9C/Cg2
C14–H14/Cg2
ꢁ x, ꢁy, 1 ꢁ z
ꢁ x, ꢁy, 1 ꢁ z
x, 1/2 ꢁ y, 1/2 + z
(3)
C3–H3/O1
X-ray
0.93
1.08
0.97
1.08
2.44
2.30
2.77
2.69
3.345(9)
3.345(9)
3.593(3)
3.593(3)
3.947(2)
163
162
142
141
ꢁ1 + x, y, z
Norm-H
X-ray
Norm-H
C11–H11B/Cg1
1 ꢁ x, 2 ꢁ y, ꢁz
Cg1/Cg1
a
Cg1 and Cg2 are the centroid of the C1–C6 and C12–C17 rings, respectively. Norm-H are the neutron normalized distances.
840 | CrystEngComm, 2012, 14, 837–846
This journal is ª The Royal Society of Chemistry 2012

View Article Online
Fig. 1 Molecular views of C10H12O3 (1), C17H18O3 (2) and C14H18O5 (3).
mechanical calculations agrees well with that observed from the
X-ray structural studies. The geometry optimized structure in 2
shows a rotation of the phenyl ring (C12–C17) about the C11–
C12 bond when compared with the crystallographic analysis.
The r.m.s. deviations between the geometrically optimized bond
lengths and bond angles (Table 2) and the corresponding crys-
ꢀ
ꢀ
ꢀ
tallꢀographically determined values are 0.016 A, 2.6 in 1, 0.025 A,
ꢀ
ꢀ
1.8 in 2, and 0.019 A, 2.6 in 3. The small differences between the
observed and calculated geometrical parameters in 1–3 can be
attributed to the fact that theoretical calculations have been
carried out with isolated molecules in the gaseous phase whereas
the experimental values correspond to the crystalline state, in
which intermolecular interactions play a significant role. The
atomic charges estimated from Mulliken population analysis
appear to be consistent with the electronegativity of the
constituent atoms. The net charges on O2 (ꢁ0.510 in 1, ꢁ0.515 in
2 and ꢁ0.514 in 3), O1 (ꢁ0.494 in 1, ꢁ0.433 in 2 and ꢁ0.431 in 3)
and O3 (ꢁ0.456 in 1, ꢁ0.504 in 2 and ꢁ0.494 in 3) suggest that
more negative charge is received by the atom O2 than O1 and O3.
Moreover, the unsubstituted hydroxyl O3 atom in compound 1 is
less electronegative than that in compounds 2 and 3 where the
hydroxyl group is substituted by a phenylmethoxy moiety in 2
and an ethyl-2-hydroxyacetate group in 3.
A network of C–H/O, C–H/p hydrogen bonds and p/p
interactions (Table 3) connects the molecules of 1–3 into supra-
molecular frameworks. The histogram of C(sp2)–H/O and C
(sp3)–H/O hydrogen bond distances (Fig. 4) based on structures
extracted from the CSD indicates that the intermolecular C–H.
O distances in 1–3 lie in the bins having high population. Inter-
molecular C3–H3/O1 hydrogen bonds connect the molecules of
1 to form C11(6) chains39 propagating along the [010] direction.
The polymeric chains are further linked via intermolecular C9–
H9B/O3 hydrogen bonds, thus forming a R44(24)39 synthon of
4
ꢀ
ꢀ
dimension 5.8 A ꢂ 13.8 A (Fig. 5). The R4(24) rings are edge-
fused to generate a two-dimensional molecular assembly in the
(110) plane (Fig. 5). The parallel molecular sheets in 1 are stacked
along the crystallographic c-axis with an interplanar separation
ꢀ
of 3.3 A. A pair of intermolecular C–H/O hydrogen bonds
Fig. 2 Final Rietveld refinement plots of C10H12O3 (1), C17H18O3 (2)
and C14H18O5 (3).
Fig. 3 Superposition of molecular conformations as obtained from the
X-ray analyses (red), and DFT calculations (blue).
This journal is ª The Royal Society of Chemistry 2012
CrystEngComm, 2012, 14, 837–846 | 841

View Article Online
Fig. 4 A distance histogram of C(sp2/sp3)/O contacts in organic structures in the CSD.
(Table 3) in 2 with the methoxy C9 atom acting as a donor to the
O2 atom produces a centrosymmetric R22(6) dimeric ring (M)
centred at (ꢁ1/2, 0, 1/2), Fig. 6. Similarly, another pair of
intermolecular C11–H11A/O1 hydrogen bonds in 2 intercon-
nects molecules forming a centrosymmetric R22(14) dimeric ring
(N) centred at (0, 0, ꢁ1/2). The R22(6) and R22(14) rings in 2 are
alternately linked into a step like MNMN. architecture with
a graph set notation36 of C22(16)[R22(6)][R22(14)] (Fig. 6a). Further
linking between the molecular steps in 2 is provided by C–H/p
hydrogen bonds (Table 3, Fig. 6b), so generating a three-
dimensional supramolecular network (Fig. 6c). In 3, an inter-
molecular C3–H3/O1 hydrogen bond generates a C11(6) chain
running along the [100] direction (Fig. 7, shown in green dotted
lines). Antiparallel C11(6) chains are joined via C–H/p(arene)
hydrogen bonds to form a columnar assembly along the [100]
direction (Fig. 7, shown in blue dotted lines). An interplanar
ꢀ
spacing of 3.370(2) A with a ring-centroid separation of 3.947(2)
ꢀ
ꢀ
A and a ring offset of 2.01 A indicates a possible p/p interac-
tion between the parallel phenyl (C1–C6) rings in 3. The
increased centroid–centroid separation in 3 compared to the
normal p/p interaction range of 3.3–3.8 A40 can be rationalized
ꢀ
on the grounds that phenyl rings are polarized by electron-
donating substituents, methoxy and O–(methylcarboethoxy),
which increase the p-electron repulsion. The p/p interaction
provides the necessary linking among the columns in 3 along the
[010] direction to produce a two-dimensional supramolecular
framework in the (110) plane (Fig. 7, shown in black dotted
lines).
Fig. 5 The molecular packing of C10H12O3 (1) showing the formation of a two-dimensional supramolecular assembly in the (110) plane. For the sake of
clarity, H-atoms not involved in hydrogen bonding have been omitted.
842 | CrystEngComm, 2012, 14, 837–846
This journal is ª The Royal Society of Chemistry 2012

View Article Online
Fig. 6 (a) The formation of a step like MNMN. architecture with a graph set notation of C22(16)[R22(6)][R22(14)] in C17H18O3 (2). (b) The one
dimensional chain formed via C–H/p hydrogen bonds in C17H18O3 (2). (c) A three-dimensional supramolecular network in C17H18O3 (2).
The Hirshfeld surfaces of 1–3 are illustrated in Fig. 8a,
showing surfaces that have been mapped over a dnorm range of
with O atoms of acetaldehyde, methoxy and phenolic groups),
the lower spike ‘b’ being an acceptor spike (O atoms of CH3CO,
OCH3 and OH groups interacting with the H atoms of CH
parts). The wings (Fig. 8b, marked with black circles) in the (di,
ꢀ
ꢁ0.5 to 1.5 A. The dominant interactions between CH and O
atoms in 1–3 can be seen in the Hirshfeld surface as the bright red
areas marked as ‘a’ and ‘b’ in Fig. 8a. The light red spots labelled
as ‘c’ for 2 and 3 are due to C–H/p interactions (Fig. 8a). Other
visible spots in Fig. 8a correspond to H/H contacts. The cor-
responding 2D fingerprint plots (Fig. 8b) exhibit characteristic
spikes labelled as ‘a’ and ‘b’. The upper spike ‘a’ in Fig. 8b
represents the donor spike (phenyl and methyl CH interacting
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
de) regions of (1.6 A, 1.0 A) and (1.0 A, 1.6 A) in 2, and (2.0 A, 1.2
ꢀ
ꢀ
ꢀ
A) and (1.2 A, 2.0.A) in 3 correspond to the C–H/p interactions
(Table 3). The high density of red points in the (di, de) regions of
ꢀ
ꢀ
(1.8 A, 1.8 A) in the fingerprint plot of 3 indicates the presence of
p/p interactions. The subtle difference among the molecular
interactions in 1–3 is reflected in the distribution of scattered
This journal is ª The Royal Society of Chemistry 2012
CrystEngComm, 2012, 14, 837–846 | 843

View Article Online
Fig. 7 A two-dimensional supramolecular framework in the (110) plane in C14H18O5 (3) formed by a combination of C–H/O (green dotted line), C–
H/p (blue dotted line) and p/p (black dotted line) interactions.
points in the high (di, de) region in the plots (Fig. 8b), which
ꢀ
the Hirshfeld surfaces in 1–3 as well as a few hydrox-
yacetophenone derivatives retrieved from the CSD (Fig. 9)
indicated that the H/H contacts contributed about 50% (50.6%
ꢀ
spreads upto di¼ de ¼ 2.0 A in 1, di¼ de ¼ 2.3 A in 2 and di ¼ de ¼
ꢀ
2.1 A in 3. The relative contributions of different interactions to
Fig. 8 (a) Hirshfeld surfaces and (b) fingerprint plots for C10H12O3 (1), C17H18O3 (2) and C14H18O5 (3).
844 | CrystEngComm, 2012, 14, 837–846
This journal is ª The Royal Society of Chemistry 2012

View Article Online
Fig. 9 The relative contributions of various intermolecular contacts to the Hirshfeld surface area in C10H12O3 (1), C17H18O3 (2), C14H18O5 (3), and
some related structures retrieved from the CSD.
in 1, 54.6% in 2 and 3) to the Hirshfeld surface area, while the
remaining 50% contributions were mostly due to O/H (26.1% in
1, 16.4% in 2 and 28.3% in 3) and C/H (17.5% in 1, 24.7% in 1
and 22.2% in 3) contacts with only a minor contribution from
C/C close contacts (2.4% in 1, 2.5% in 2 and 2.1% in 3). With
different substituents at the o-hydroxyacetophenone ring 4 and 5
positions, the contribution of H/H contacts to the Hirshfeld
surface increases steadily from 15.0% in DEKYOI12 to 54.6% in 2
and 3 with a corresponding decrease of O/H interactions from
55.1% in DEKYIC0111 to 16.4% in 2. The contribution of C–H/
p hydrogen bonds, which appear as C/H contacts in the
Hirshfeld surface, varies from 24.7% in 2 to 8.4% in VOXPED.15
The enhanced contribution of O/H interactions in VOXPED15
(43.6%), DEKYOI12 (47.6%) and DEKYIC0111 (55.1%) can be
attributed to the fact that these molecules contain multiple OH
and/or NO2 functionalities. Fig. 9 also indicates that H/H, O/
H and C/H contacts can account for 80–95% of the Hirshfeld
surface area in these class of compounds.
Schweitzer41 that in the absence of classical hydrogen bonding
synthons ‘‘the structure is held together by whatever factors
contribute to the cohesive energies’’ of specified pairs of
molecules.
Acknowledgements
Financial support from the University Grants Commission, New
Delhi, through the DRS (SAP-II) program for purchasing the X-
ray powder diffractometer in the Department of Physics,
Jadavpur University, is gratefully acknowledged.
References
1 (a) G. R. Desiraju, The Crystal as a Supramolecular Entity, John
Wiley & Sons, Chichester, 1996; (b) N. A. J. M. Sommerdijk,
Angew. Chem., Int. Ed., 2003, 42, 3572–3574; (c) D. B. Amabilino
and J. F. Stoddart, Chem. Rev., 1995, 95, 2725–2828; (d)
C. G. Claessens and J. F. Stoddart, J. Phys. Org. Chem., 1997, 10,
254–272.
2 (a) L. J. Prins, D. N. Reinhoudt and P. Timmerman, Angew. Chem.,
Int. Ed., 2001, 40, 2382–2426; (b) G. R. Desiraju, Nature, 2001, 412,
397–400; (c) F. H. Allen, W. D. S. Motherwell, P. R. Raithby,
G. P. Shields and R. Taylor, New J. Chem., 1999, 23, 25–34; (d)
V. Sethuraman, N. Stanley, P. T. Muthiah, W. S. Sheldrick,
M. Winter, P. Luger and M. Weber, Cryst. Growth Des., 2003, 3,
823–828.
3 (a) G. R. Desiraju, Acc. Chem. Res., 2002, 35, 565–573; (b)
S. Takahashi, T. Jukurogi, T. Katagiri and K. Uneyama,
CrystEngComm, 2006, 8, 320–326; (c) C. S. Lai, F. Mohr and
E. R. T. Tiekink, CrystEngComm, 2006, 8, 909–915.
4 (a) R. Banerjee, G. R. Desiraju, R. Mondal and J. A. K. Howard,
Chem.–Eur. J., 2004, 10, 3373–3383; (b) G. R. Desiraju and
T. Steiner, The Weak Hydrogen Bond in Structural Chemistry and
Biology, Oxford University Press, Oxford, U.K., 1999; (c)
B. Moulton and M. J. Zaworotko, Chem. Rev., 2001, 101, 1629–1658.
5 A. Nangia and G. R. Desiraju, Acta Crystallogr., Sect. A: Found.
Crystallogr., 1998, 54, 934–944.
6 C. Glidewell, J. N. Low, J. M. S. Skakle, S. M. S. V. Wardell and
J. L. Wardell, Acta Crystallogr., Sect. B: Struct. Sci., 2005, 61, 227–
237.
Conclusions
The results of the crystal structure determination using X-ray
powder diffraction of three o-hydroxyacetophenone derivatives
(1–3), in which the hydroxyl group in 1 is replaced by a phenyl-
methoxy moiety in 2, and a ethyl-2-hydroxyacetate group in 3,
clearly demonstrate the role of weak hydrogen bonds and p/p
interactions in building supramolecular assemblies. The avail-
ability of phenyl/methyl C atoms, acetaldehyde O atoms and
aromatic p-systems in the compounds provides scope for a range
of intermolecular interactions. The subtleties of crystal packing
are illustrated by the variations in the structures due to the
interplay of weak hydrogen bonds forming polymeric chains or
dimeric rings, which then assemble differently into a two
dimensional sheet in 1, a three-dimensional framework in 2 and
a columnar architecture in 3. The relative contribution of
different interactions to the Hirshfeld surfaces indicated that the
H/H and O/H contacts can account for more than 70%
(76.7% in 1, 71.0% in 2 and 82.9% in 3) to the Hirshfeld surface
area, while the remaining contributions are mostly due to C/H
interactions. The series of compounds investigated here allows us
to understand the influence of weak intermolecular forces in
building supramolecular frameworks in the solid state. This
scenario is consistent with the idea proposed by Dunitz and
7 (a) M. Nishio, M. Hirota and Y. Umezawa, The CH/p Interaction:
Evidence, Nature and Consequences, Wiley, New York, 1998; (b)
M. Nishio, CrystEngComm, 2004, 6, 130–158.
8 (a) A. Drelinkiewicza, A. Waksmundzka, J. W. Makowski, A. Krol
and A. Zie,ba, Catal. Lett., 2004, 56, 143–156; (b) L. Favier,
C. Tonn, E. Guerreiro, A. Rotelli and L. Pelzer, Planta Med., 1998,
64, 657–659; (c) P. Huang, S. Won, S. Day and C. Lin, Helv. Chim.
Acta, 1999, 82, 1716–1727; (d) A. Sala, M. C. Recio, R. M. Giner,
ꢁꢂ
S. Manez and J. L. Rıos, J. Nat. Prod., 2001, 64, 1360–1362; (e)
F. J. Brown, P. R. Bernstein, L. A. Cronk, D. L. Dosset,
ꢃ
This journal is ª The Royal Society of Chemistry 2012
CrystEngComm, 2012, 14, 837–846 | 845

View Article Online
K. C. Hebbel, T. P. Maduskuie Jr., H. S. Shapiro, E. P. Vacek and
Y. K. Yee, J. Med. Chem., 1989, 32, 807–826.
22 A. A. Coelho, Topas User Manual, Version 3.1., Bruker AXS GmbH,
Karlsruhe, Germany, 2003.
9 F. H. Allen, Acta Crystallogr., Sect. B: Struct. Sci., 2002, 58, 380–388.
10 E. Wajsman, M. J. Grabowski, A. Stepien and M. Cygler, Cryst.
Struct. Commun., 1978, 7, 233–236.
11 A. Filarowski, A. Kochel, P. E. Hansen, A. Urbanowicz and
K. Szymborska, J. Mol. Struct., 2007, 844–845, 77–82.
12 M. West-Nielsen, P. M. Dominiak, K. Wozniak and P. E. Hansen, J.
Mol. Struct., 2006, 789, 81–91.
13 E. Wajsman, M. J. Grabowski, A. Stepien and M. Cygler, Acta
Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem., 1981, 37,
1458–1459.
23 A. Boultif and D. Louer, J. Appl. Crystallogr., 2004, 37, 724–731.
24 A. Altomare, R. Caliandro, M. Camalli, C. Cuocci, C. Giacovazzo,
A. G. G. Moliterni and R. Rizzi, J. Appl. Crystallogr., 2004, 37,
1025–1028.
25 A. Le Bail, H. Duroy and J. L. Fourquet, Mater. Res. Bull., 1988, 23,
447–452.
26 H. J. Toraya, J. Appl. Crystallogr., 1986, 19, 440–447.
27 J. Baldinozzi and J. F. Berar, J. Appl. Crystallogr., 1993, 26, 128–129.
28 V. Favre-Nicolin and R. Cerny, J. Appl. Crystallogr., 2002, 35, 734–
743, http://objcryst.sourceforge.net.
14 F. A. Macias, D. Chinchilla, J. M. G. Molinillo, F. R. Fronczek and
K. Shishido, Tetrahedron, 2008, 64, 5502–5508.
29 J. J. P. Stewart, MOPAC 5.0, A General Purpose Molecular Orbital
Package (QCEP 455).
15 M. K. Kokila, K. A. Nirmala, Puttaraja and N. Shamala, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 1992, 48, 1133–1134.
16 W.-X. Qing, Y.-Z. Liu and S.-M. Yao, Acta Crystallogr., Sect. E:
Struct. Rep. Online, 2009, 65, o2004.
17 (a) W. I. F. David and K. Shankland, Acta Crystallogr., Sect. A:
Found. Crystallogr., 2008, 64, 52–64; (b) Structure Determination
from Powder Diffraction Data, W. I. F. David, K. Shankland, L. B.
McCusker, Ch. Baerlocher, ed., Oxford University Press, New
York, 2002; (c) S. Pagola, P. W. Stephens, D. S. Bohle,
A. D. Kosar and S. K. Madsen, Nature, 2000, 404, 307–310; (d)
K. D. M. Harris and E. Y. Cheung, Chem. Soc. Rev., 2004, 33,
526–538.
30 A. C. Larson and R. B. Von Dreele, General Structure Analysis
System (GSAS), Los Alamos National Laboratory Report LAUR,
2000, 86.
31 H. Toby, J. Appl. Crystallogr., 2001, 34, 210–213.
32 A. L. Spek, Acta Crystallogr., Sect. D: Biol. Crystallogr., 2006, 65,
148–155.
33 B. Delley, J. Chem. Phys., 1990, 92, 508–517.
34 J. P. Perdew, K. Burke and M. Ernzerhof, Phys. Rev. Lett., 1996, 77,
3865–3868.
35 (a) A. D. Becke, Phys. Rev. A: At., Mol., Opt. Phys., 1988, 38, 3098–
3100; (b) A. C. Lee, W. Yang and R. G. Parr, Phys. Rev. B, 1988, 37,
785–789.
18 (a) A. Bhattacharya, K. Kankanala, S. Pal and A. K. Mukherjee, J.
Mol. Struct., 2009, 975, 40–46; (b) S. Takeya, K. A. Udachin,
I. L. Moudrakovski, R. Susilo and J. A. Ripmeester, J. Am. Chem.
Soc., 2010, 132, 524–531; (c) K. Fujii, H. Uekusa, M. Fukano and
H. Koshima, CrystEngComm, 2011, 13, 3197–3201; (d)
B. Chattopadhyay, S. Basu, P. Chakraborty, S. K. Choudhuri,
A. K. Mukherjee and M. Mukherjee, J. Mol. Struct., 2009, 932, 90–96.
19 (a) D. Albesa-Jove, B. M. Kariuki, S. J. Kitchin, L. Grice,
E. Y. Cheung and K. D. M. Harris, ChemPhysChem, 2004, 5, 414–
36 (a) M. A. Spackman and D. Jayatilaka, CrystEngComm, 2009, 11, 19–
32; (b) F. L. Hirshfeld, Theor. Chim. Acta, 1977, 44, 129–138; (c)
H. F. Clausen, M. S. Chevallier, M. A. Spackman and
B. B. Iversen, New J. Chem., 2010, 34, 193–199.
37 (a) A. L. Rohl, M. Moret, W. Kaminsky, K. Claborn, J. J. McKinnon
and B. Kahr, Cryst. Growth Des., 2008, 8, 4517–4525; (b) A. Parkin,
G. Barr, W. Dong, C. J. Gilmore, D. Jayatilaka, J. J. McKinnon,
M. A. Spackman and C. C. Wilson, CrystEngComm, 2007, 9, 648–
652; (c) M. A. Spackman and J. J. McKinnon, CrystEngComm,
2002, 4, 378–392.
€
418; (b) J. van de Streek, J. Bruning, S. N. Ivashevskaya,
M. Ermrich, E. F. Paulus, M. Bolte and M. U. Schmidt, Acta
Crystallogr., Sect. B: Struct. Sci., 2009, 65, 200–211; (c) J. B. van
Mechelen, R. Peschar and H. Schenk, Acta Crystallogr., Sect. B:
Struct. Sci., 2006, 63, 1121–1130; (d) J. B. van Mechelen,
R. Peschar and H. Schenk, Acta Crystallogr., Sect. B: Struct. Sci.,
2006, 63, 1131–1138.
38 S. K. Wolff, D. J. Grimwood, J. J. McKinnon, D. Jayatilaka and
M. A. Spackman, Crystal Explorer 2.0, University of Western
Australia, Perth, Australia, 2007, http://hirshfeldsurfacenet.
blogspot.com/.
39 (a) M. C. Etter, Acc. Chem. Res., 1990, 23, 120–126; (b) J. Bernstein,
R. E. Davis, L. Shimoni and N. L. Chang, Angew. Chem., Int. Ed.
Engl., 1995, 34, 1555–1573.
20 S. K. Sabui and R. V. Venkateswaran, Tetrahedron, 2003, 59, 8375–
8381.
21 F. M. Hauser and D. Ganguly, J. Org. Chem., 2000, 65, 1842–1849.
40 C. Janiak, J. Chem. Soc., Dalton Trans., 2000, 3885–3896.
41 J. D. Dunitz and W. B. Schweizer, CrystEngComm, 2007, 9, 266–269.
846 | CrystEngComm, 2012, 14, 837–846
This journal is ª The Royal Society of Chemistry 2012